Studies on the origin of anemia in chronic disease will focus on the anemia associated with cancer as an aberration in the control of erythropoiesis by T-lymphocytes during the development neoplasia. Using a Lewis lung carcinoma, the relationship of tumor induced T-suppressor cell activity and erythroid cell development will be evaluated. Using the drug cimetidine, the role of immunotherapy to block suppressor cell activity and allow the normal development of erythroid cells in tumor bearing mice will be examined. The ability of normal physiological regulators of hemopoiesis to induce differentiation in human leukemia cell lines will be examined. In vivo, K562 and HL-60 cells will be seeded into diffusion chambers and implanted into the peritoneal cavities of normal and hematologically perturbated mice. In vitro studies will focus on the ability of the bone marrow stroma of normal human donors, which appears to play an important role in normal blood cell development, to induce leukemic cell differentiation. Morphological and functional maturation will be assessed in both studies. Finally, the ability of human leukemic cell lines to suppress normal hemopoiesis prior to and after inducing differentiation by chemical agents will be examined in vitro. The objective will be to determine whether the property of leukemic cell inhibition of normal hemopoiesis is lost when leukemic cells undergo differentiation. The efficacy of "induction chemotherapy" as a means of reversing leukemic cell suppression of normal stem cell development may thus provide an alternative to cytotoxic reduction therapy to establish remission and cure.